SUMMARY OF CURRENTLY FUNDED PROJECT (1 R21 AG058181-01A1) Resistance Exercise and Low-Intensity Physical Activity Breaks in Sedentary Time to Improve Skeletal Muscle and Cardiometabolic Health in Older Adults ? REALPA Breaks in Sedentary Time Pilot Study Although awareness of the detrimental impact that sedentary behavior has on skeletal muscle and cardiometabolic health has increased over the last 20 years, more than 60% of older adults remain sedentary for greater than 8 hours per day. Moreover, 80% to 90% of adults 60 years of age or older do not meet the current public health guidelines for aerobic exercise (AE) or resistance exercise (RE) based physical activity (PA). Collectively, these adverse health behaviors contribute to the development of multiple chronic medical conditions commonly afflicting older adults, including type 2 diabetes, cardiovascular disease, sarco/dynapenia, frailty, and premature mortality. Emerging evidence suggests that breaking up sedentary time with light intensity PA (LPA) improves muscle and cardiometabolic health. Recent data also suggest that RE combined with moderate intensity AE effectively improves muscle and cardiometabolic health in older adults. However, the impact that RE combined with LPA breaks in sedentary time has on muscle and cardiometabolic health in older adults remains unknown. The overall objective of this pilot study is to determine the effect of 16 weeks of RE alone or RE combined with LPA breaks in sedentary time on muscle and cardiometabolic health. The central hypothesis is that the addition of LPA breaks in sedentary time will enhance RE-induced improvements in muscle and cardiometabolic health in sedentary older adults. Our overall approach to test our central hypothesis is to recruit and study 36 physically inactive community dwelling older adults (65-80 years) who are randomized to 16 weeks of either (i) RE (2 x/wk), (ii) RE (2 x/wk) and LPA breaks in sedentary time (5 d/wk, 6x10 min breaks per day at 2 METS, ~500 kcal/wk above resting metabolism), or (iii) RE (2 x/wk) and moderate intensity AE (3 d/wk, 50 min/session at 4 METS, ~500 kcal/wk above resting metabolism). The effect that these PA interventions have on muscle health will be measured by changes in muscle strength, mass, and quality (strength/mass) using isokinetic dynamometry and dual-x-ray absorptiometry (DXA) (primary outcomes). In addition, improvements in muscle oxidative capacity will be measured using high-resolution respirometry and oxidative damage to muscle proteins by immunoblotting (secondary outcomes). The effect that these PA interventions have on cardiometabolic health will be measured by changes in body composition by DXA, fasting blood glucose and lipids by a clinical chemistry panel and glucose tolerance by a mixed meal tolerance test (primary outcomes). Additionally, improvements in immunometabolic health will be measured by changes in low-grade systemic inflammation (e.g., TNF?) using immunoassays and immune cell oxidative capacity by high-resolution respirometry (secondary outcomes). The proposed studies will provide preliminary evidence that LPA breaks in sedentary time enhance RE- induced improvements in muscle and cardiometabolic health in older adults, will further evaluate efficacy in a follow-up R01 randomized clinical trial.